NMDA receptor modulator9 is an orally active positive allosteric modulator (PAM) of the NMDA receptor. It enhances the activity of the GluN2A receptors. In a chronic restraint stress (CRS) induced depression mouse model, NMDA receptor modulator9 exhibits significant antidepressant-like effects. It is used for research on depression.

NMDA receptor modulator 9 (Compound Y36) at 30 μM significantly enhances currents mediated by GluN2A receptors in Xenopus laevis oocytes expressing GluN1/GluN2A, but only when co-administered with glutamate and glycine (Glycine). It demonstrates higher efficacy (E max = 397.7%) compared to GNE-3419 (E max = 196.4%), reducing the EC 50 value for glutamate/glycine on the GluN2A receptor and increasing the E max value. At a concentration of 200 μM, NMDA receptor modulator 9 does not exhibit significant cytotoxicity in HEK293, PC12, and SH-SY5Y cell lines. Its affinity for the hERG channel is low, with an IC 50 of 67.85 μM, indicating a low risk of cardiotoxicity.

NMDA receptor modulator 9 (Compound Y36) administered at doses of 0.1-1.0 mg/kg, either intraperitoneally or orally, in a single dose, alleviates depression-like behavior in chronic restraint stress (CRS) mice. At doses of 200-350 mg/kg, orally administered in male C57BL/6J mice, it shows gradual lethality, with an LD50 of 270.82 mg/kg. When given at 0.3-1.0 mg/kg intraperitoneally every two days over 30 days in ICR mice, it does not cause abnormal behavior, maintains stable body weight, shows no significant changes in organ/body weight ratios, and does not result in evident nephrotoxicity, hepatotoxicity, or cardiac damage.